Download Ascorbic Acid in the Prevention and Treatment of Cancer

Ascorbic Acid in the Prevention and
Treatment of Cancer
by Kathleen A. Head, N.D.
Abstract
Proposed mechanisms of action for ascorbic acid (ascorbate, vitamin C) in the
prevention and treatment of cancer include enhancement of the immune system,
stimulation of collagen formation necessary for “walling off” tumors, inhibition of
hyaluronidase which keeps the ground substance around the tumor intact and prevents
metastasis, prevention of oncogenic viruses, correction of an ascorbate deficiency often
seen in cancer patients, expedition of wound healing after cancer surgery, enhancement
of the effect of certain chemotherapy drugs, reduction of the toxicity of other
chemotherapeutic agents such as Adriamycin, prevention of free radical damage, and
neutralization of carcinogenic substances. Scottish as well as Japanese studies have
pointed to the potential benefit of high dose vitamin C for the treatment of “terminal”
cancer. Mayo Clinic studies, however, have contradicted the Scottish and Japanese
findings, resulting in accusations of methodological flaws from both sides. Numerous
epidemiological studies have pointed to the importance of dietary and supplemental
ascorbate in the prevention of various types of cancer including bladder, breast, cervical,
colorectal, esophageal, lung, pancreatic, prostate, salivary gland, stomach, leukemia,
and non-Hodgkin’s lymphoma.
(Altern Med Rev 1998;3(3):174-186)
Introduction
In the mid-18th century, James Lind first demonstrated that the juice of fresh citrus
cures scurvy. The active agent, the enolic form of 3-keto-L-gulofurnlactone, or ascorbic acid,
was isolated in the late 1920s by Albert Szent-Gyorgyi (see figure 1). By the mid-1930s, methods had been devised to synthesize ascorbic acid, making it widely available at low cost. In the
1990s, it is the most commonly used single supplement in the U.S.1
In 1954, W.J. McCormick, a Canadian physician, formulated the hypothesis that cancer
is a collagen disease, secondary to a vitamin C deficiency.2 While alternative cancer treatments,
such as The Gerson therapy, have been incorporating diets high in vitamin C for many years,
the use of vitamin C supplementation in large doses for the prevention and treatment of cancer
was further advanced in 1971 by Linus Pauling, PhD, and Ewan Cameron, MD. A discussion of
their use of high-dose vitamin C for treatment of patients with advanced cancer can be found
below. Since 1971, considerable attention has been paid to vitamin C and cancer, particularly in
Kathi Head, N.D.—Technical Advisor, Thorne Research, Inc.; Associate Editor, Alternative Medicine Review.
Correspondence address: P.O. Box 25, Dover, ID 83825, e-mail: [email protected]
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Copyright©1998 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission
of hyaluronidase, keeping the ground substance around the tumor intact and preventing
metastasis;4 (4) inhibition of oncogenic viruses; (5) correction of an ascorbate deficiency,
often seen in cancer patients; (6) expedition
Biochemistry of Ascorbic Acid
of wound healing after cancer surgery;5 (7) enAscorbic acid is widely distributed in
hancement of the effect of certain chemoplants, its concentration varying from 0.01
therapy drugs, such as tamoxifen, cisplatin,
percent in apples to about 1 percent in rose
DTIC and others;6-8 (8) reduction of the toxichips and citrus. It is one of the most important
ity of other chemotherapeutic agents, such as
reducing agents occurring in living tissue.
Adriamycin;9 (9) prevention of cellular free
While most animals synthesize their own viradical damage;10 and (10) neutralization of
tamin C, humans and a few other animals, such
carcinogenic substances.11
as non-human primates, guinea pigs, and fruit
Taking a closer look at
bats do not. Ascorbate acthe
phenomenon of hyalucelerates hydroxylation reronidase
inhibition
actions, in part by donatFigure 1. Structure of Ascorbic Acid. Cameron, Pauling and
ing electrons to metal ion
Leibovitz wrote in
cofactors of hydroxylase
CH2OH
“Ascorbic Acid and Canenzymes. Hydroxylation
cer: A Review”: ...“the
reactions are important in
O
dangerous features of neoHOCH
O
collagen synthesis, converplastic cell behavior (invasion of lysine to carnitine,
HC
C
siveness, selective nutriconversion of dopamine to
tion, and perhaps growth)
norepinephrine, and in tyare caused by microenviC
C
rosine metabolism. Ascorronmental depolymerizabate is also utilized to cataHO
OH
tion. In turn, this matrix
lyze other enzymatic reacdestabilization is brought
tions, such as amidation
about by constant exponecessary for maximum
sure to lysosomal glycosidases continually reactivity of the hormones oxytocin, vasopressin,
3
leased by the neoplastic cells. Finally, ascorcholecystokinin, and alpha-melanotropin.
bate is involved in the natural restraint of this
Ascorbic acid is a water-soluble, chaindegradative enzyme activity.”12
breaking antioxidant which reacts directly with
Proper collagen formation is an
singlet oxygen, hydroxyl, and superoxide radiimportant
factor in the encapsulation of tumors
cals. It also may react with tocopheroxy radior the slowing of metastasis via the
cals to regenerate vitamin E.1 Conversely,
development of an almost impermeable barrier
ascorbyl radicals are quenched by vitamin E.
(known as the schirrus response). Ascorbic
acid plays an important role in collagen
Mechanisms of Action
synthesis and stability. A lack of ascorbate
Proposed mechanisms of vitamin C
significantly reduces hydroxylation of proline
activity in the prevention and treatment of canand lysine to hydroxyproline and
cer include: (1) enhancement of the immune
hydroxylysine, respectively, jeopardizing
system by increased lymphocyte production;
proper collagen cross-linking. This leads to
(2) stimulation of collagen formation, necesinstability of the triple helix of collagen which,
sary for “walling off” tumors; (3) inhibition
Alternative Medicine Review ◆ Volume 3, Number 3 ◆ 1998
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Vitamin C & Cancer
the area of prevention. However, there has
been a paucity of human studies using vitamin C to treat already existing cancer.
Number of Survivors, %
Figure 2. A comparison of survival times in ascorbate-treated
patients and matched controls. Adapted from
Cameron and Pauling.16
exceptions. In preliminary studies
which began in November 1971,
80
a small group of patients with advanced cancer were given 10
Patients Receiving Ascorbate
70
67%
grams of sodium ascorbate daily.
Controls
The initial testing was an uncon60
53%
trolled study, conducted on 50
patients. Seventeen of these pa50
tients exhibited seemingly no re40
sponse, 10 a minimal response, 11
36%
retardation of the tumor growth,
30
28%
3 ceasing of the tumor growth, 5
regression of tumor growth with
18%
20
16%
12%
long-term survival, and 6 experi11%
10
enced hemorrhage and necrosis of
7%
2.5%
1.7%
the tumors, which destroyed the
0.3%
tumors but killed the patients in
50 100 150 200 250 300 350 400 450 500 550 600
the process.13 An evaluation of the
Time of Survival, Days
life expectancy of these first 50
“terminally ill” patients treated
with
ascorbate
yielded promising results.
in turn, results in increased collagen
Based on data from previous similar groups
catabolism. In vitro, vitamin C also has been
of patients, it was expected that 90 percent of
found to increase collagen synthesis by
12
the group would be dead within three months
fibroblasts.
of being labeled “terminal.” When 10 g ascorCancer patients tend to be immunobate was prescribed daily (beginning at the
compromised, demonstrating low lymphocyte
time the patient was labeled “terminal”), by
ascorbate levels. The immune surveillance
the 100th day of treatment the mortality rate
system is important, both in inhibiting the iniwas only 50 percent. Of the remaining 25 patiation phase of cancerous growth, and also in
tients, 20 died between days 110 and 659, with
the prevention of spread. Ascorbate supplean average survival time of 261 days; and five
mentation increases the number and effectivehad an average survival time of greater than
ness of lymphocytes and enhances phagocy12
610 days.14
tosis.
Subsequently, a controlled retrospective
study
was conducted, comparing survival
Vitamin C in the Treatment of
times of 100 terminally ill cancer patients at
Cancer
Vale of Leven Hospital with 1,000 matched
The Vale of Leven Studies: Most of
controls from the same hospital. The patients
the studies on vitamin C and cancer relate to
were randomly selected from the database of
its protective effect, rather than use of the vithose terminal cancer patients who had retamin for the treatment of active cancer. The
ceived ascorbate. Each ascorbate-treated paVale of Leven studies conducted by Ewan
tient was matched with 10 controls from the
Cameron, MD and his associates, (later includsame hospital of the same age, sex, and type
ing Linus Pauling, PhD), at his hospital in Loch
and stage of cancer who had not been preLomondside, Scotland, are among the few
scribed vitamin C. In 90 percent of the cases,
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improvements included a decrease in malignant ascites and pleural effusion, relief from
hematuria, some reversal of hepatomegaly and
jaundice, and decreases in erythrocyte SED
rate and serum seromucoid levels, all accepted
indicators of a decrease in malignant activity.14
Furthermore, patients who had been on large
doses of narcotics, such as morphine, for pain
relief, showed none of the typical withdrawal
symptoms.
Based on the above cited studies the
researchers concluded: “It is our conclusion
that this simple and safe treatment, the ingestion of large amounts of vitamin C, is of definite value in the treatment of patients with
advanced cancer. Although the evidence is as
yet not so strong, we believe that vitamin C
has even greater value for the treatment of
cancer patients with the disease in earlier
stages and also for the prevention of cancer.”18
The Vale of Leven protocol called for
a ten-day course via intravenous (IV), continuous slow-drip infusion of sodium ascorbate in
half-strength Ringer’s Lactate Solution. After
the IV treatment, assuming the patient was able
to take medication by mouth, an oral dose of
vitamin C was begun at a dose of 2.5 grams
every 6 hours for a total of 10 grams in 24
hours. The dosage varied somewhat, ranging
from 10-30 grams daily, and was continued
indefinitely. The goal was to maintain plasma
ascorbate levels of at least 3 mg/dl. The researchers reported generally a subjective improvement in well-being, vigor, pain relief, and
appetite was apparent within 5-7 days. Increased energy was believed to be a result of
improved carnitine synthesis with a resulting
increase in triglyceride transport into cell mitochondria.19
Japanese Studies: Uncontrolled trials
conducted at two different hospitals in Japan
during the 1970s also confirmed the increase
in survival time of terminal cancer patients
supplemented with ascorbate. At the Fukuoka
Torikai Hospital, the average survival time
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Vitamin C & Cancer
the ascorbate-treated group lived three times
longer than the control group. For the other
10 percent, long-term survival made it impossible to assess survival time with certainty, but
at the time of publication of the study, the
ascorbate group exhibited greater than 20 times
the survival rate of the control group.15(see
Figure 2)16
Having been criticized by some investigators for not assuring the subjects were randomly chosen from the same representative
subpopulations in the treated and control
groups, a second retrospective evaluation at
the Vale of Leven hospital was undertaken in
1978 – again with 100 patients receiving ascorbic acid compared to 1,000 matched controls
without vitamin C.17 Most of the ascorbatetreated group and about half the controls were
the same subjects as in the initial study. This
time, since there are different mean survival
times for different types of cancer, the groups
were further divided according to types of cancer, and controls carefully matched (see Table
1). In addition, the groups passed several “randomness” tests. In each of the nine types of
cancer the ascorbate group had a considerably
longer survival time than their matched controls. At the time of evaluation, eight patients
in the vitamin C group were still living, while
no one was alive in the control group; this resulted in 321+ days longer lifespan for the vitamin C treated group. Factoring out those in
the ascorbate group who were still living at
the time of evaluation, the vitamin C group
lived an average of 251 days longer than the
control group.
Cameron and Pauling later evaluated
the first 500 “terminal” cancer patients to receive ascorbate. In most cases, subjective improvement – increased feeling of well-being,
more energy, more alertness, decrease or elimination of pain, better appetite – were noted by
the ascorbate patients. Cameron reported a
quite dramatic relief of bone pain from metastases in four out of five patients. Objective
Table 1. Survival times: Ascorbate-treated patients vs. matched controls for various tumor
sites. Adapted from Cameron and Pauling.17
Mean survival times, days
From first
hospital attendance
Primary
tumor type
Colon
Bronchus
Stomach
Breast
Kidney
Bladder
Rectum
Ovary
Others
All
Patients, No.
From date of
untreatability
Increased survival times
of ascorbate -treated
patients, days*
A
B
C
D
E
F
Control
Test
Control
A-B
C-D
G
Test
Controls
Test
17
17
13
11
8
7
7
6
14
170
170
130
110
80
70
70
60
140
458+
219+
286+
1396+
774+
1669+
634
884
706+
316
118
159
1020
492
420
336
366
279
352+
186+
182+
487+
381+
355+
270
183
278+
33
31
32
52
39
21
43
69
37
142+
101+
127+
376+
282+
1249+
298
518
427+
319+
155+
150+
435+
342+
334+
227
114
241+
324
184+
134+
378+
348+
226+
247
157
189+
100
1000
681+
360
293+
38
321+
255+
234+
* E, calculated as A - B; F, calculated as C - D; G, additional survival time of first set of ascorbate-treated patients with first set of controls.
The + following a number indicates that one patient in the group (two in the bladder group) continued to survive after 15 May 1978.
after being labeled “terminal” was 43 days for
44 patients supplemented with low levels of
ascorbate (less than 4 grams daily), and 246
days for 55 patients supplemented with higher
dosages of ascorbate (greater than 5 grams
daily — averaging 29 grams daily) and starting at the time of “terminal” diagnosis.20 The
researchers found no differences in survival
times between the groups receiving 5-9 grams
daily and those receiving 10-29 grams daily.
A decline in effect was noted in those receiving 30-60 grams daily. They found the best
results with uterine cancer, and the smallest
increases in survival time with lung and stomach cancer.
Effectiveness of ascorbate was also
observed at the Kamioka Kozan Hospital
where 19 terminally-ill control patients survived an average of 48 days compared to six
patients on high levels of vitamin C who lived
an average of 115 days, or 2.4 times longer
than the control group.21 These researchers also
reported the improved quality of life observed
in the Scottish studies.
Mayo Clinic Studies: In an attempt to
either duplicate or refute the Cameron and
Pauling results, the Mayo Clinic initiated a test
on 150 patients.22 Subjects were randomly
divided into two groups, one group of 60
received 10 grams of ascorbic acid daily in
four divided doses while the control group of
63 received an equal number of placebo
capsules. After randomization, 27 patients
elected not to participate and comprised a third
“no treatment” group. Treatment was
continued until death or until the patient was
no longer able to take medication orally. The
two groups were evenly balanced with regard
to age, sex, tumor site, initial performance
status, and previous treatment. Fifty-eight
percent of those receiving placebo and 63
percent of those receiving ascorbate reported
subjective improvement in symptoms during
the treatment period. The researchers reported
no significant difference between the vitamin
C and placebo groups in regard to survival
time; however, the 27 patients who received
no treatment experienced a significantly lower
survival time, living an average of 25 days
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were not randomly assigned to groups ahead
of time but chosen after the fact, that selection
bias occurred, with the researchers consciously
or subconsciously selecting the ascorbatetreated patients who had the best prognosis and
outcomes to be part of the study group. The
Mayo researchers made this statement:
“Uncontrolled or historically controlled studies have a necessary purpose in the
evaluation of any therapeutic method, since
they serve to develop a hypothesis of therapeutic effectiveness. Such studies, however,
rarely prove such effectiveness, which in most
circumstances should be established by prospective randomized study. Whether one is
dealing with the treatment of the common cold
or of cancer, and whether one is dealing with
a benign vitamin or a highly toxic chemotherapy program, it would seem to serve the
interest of the patient best for public advocacy
of a proposed treatment to be withheld until
that treatment had been proved effective by
definitive studies of sound scientific design.”23
The initial Mayo study was criticized
by Pauling and Cameron as they felt the two
groups were not comparable. In the initial
Cameron study, only 4 of the 100 patients had
received prior chemotherapy or radiation,
while in the first Mayo study the majority of
patients had received prior chemotherapy. As
previously mentioned, the Mayo Clinic conducted a second study with patients who had
not received prior chemotherapy or radiation.
Regarding the second study, in a personal interview with Dr. Pauling, he told this author:24
“I have formulated three criteria for
validity of a clinical trial. The Mayo Clinic
paper fails on all three.” When asked what the
three criteria were, this is what he said: “Well,
first if you want to test something with a cohort of patients, every patient should be treated
the same way as the other patients and the same
way over the period of the trial. In the Mayo
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Vitamin C & Cancer
compared to an average of 51 days for the
vitamin C or placebo groups. All but nine of
the 123 subjects had received prior
chemotherapy, radiation, or both.
Based on other researchers’ complaints
that the Mayo study had not addressed the effect of vitamin C on cancer patients who had
not received prior chemotherapy or radiation,
a second trial was initiated by the same researchers.23 In this study, only patients with advanced colorectal cancer were included. At the
time of administration of vitamin C, the researchers deemed them all inappropriate candidates for chemotherapy. One hundred patients were randomly assigned to receive either 10 grams ascorbic acid or placebo daily.
Patients continued on the treatment for as long
as they were able to take oral medications or
until there was evidence of tumor progression.
At this point, over half of the subjects received
subsequent chemotherapy. The researchers did
not report survival times as they did not continue the patients on vitamin C until they died.
Instead, they reported that after one year 49
percent of the vitamin C group and 47 percent
of the placebo group were still living. They
reported that for both groups survival time was
comparable to the Cameron and Pauling untreated group. When they selected patients
with a bias toward those with a more favorable prognosis, they found results in both
groups similar to the Cameron and Pauling
vitamin C treated groups, implying bias selection on the part of Cameron and Pauling.
Because of the differences in study design, it
is impossible to compare the results of these
trials.
The Controversy: It is impossible to
have a discussion about vitamin C and cancer
without discussing the controversy stirred by
the Vale of Leven and Mayo studies. Both sides
accused the other of serious study flaws. The
Mayo researchers claimed that, because the
Vale of Leven studies were retrospective instead of prospective, and since the subjects
Clinic study, there were perhaps four separate
periods. There was a period when the vitamin
C patients received vitamin C every day. So
that would be like Cameron’s patients. They
received vitamin C every day. Then there was
a period when they didn’t receive vitamin C
and that would be a trial of patients during a
period after they receive vitamin C for awhile
and then stop it. Then there was a period when
they were being given chemotherapy. This was
a rather short period, maybe a month or two.
Then there was a period when they didn’t receive anything after they’d been given chemotherapy. So, there were four periods. The
first period lasted a median time of 2.5 months
and nobody died. None of the vitamin C or
control patients died. Since none of the vitamin C patients died you don’t have any mortality data similar to Cameron’s, of patients
who received vitamin C every day until their
death. So, it just doesn’t have any relation to
Cameron’s work. Then there is the period after the vitamin C or placebo was stopped. None
of the placebo patients died for some strange
reason. During this period, after stopping the
vitamin C, the vitamin C and placebo patients
died off at about the same rate. That’s perhaps
what you would expect, not expect the vitamin C given the year before to be [effective].
Then there’s no information about what happened when they started giving chemotherapy
to the patients, but about 58 out of 100 got
chemotherapy and they began dying faster than
when they weren’t getting chemotherapy. So,
that may be significant. Well, that’s the first
criteria.
“The second criteria is if you plot the
logarithm of the fraction surviving against
time, you either get a straight line or it can be
bending up, it can’t bend down unless you do
something that causes them to die. Well, theirs
bent down because they started giving them
chemotherapy.
“Thirdly, for a well-conducted study,
the death line, surviving line extrapolates back
to the origin. They had a period of 90 days
when only one patient died out of 100. They
should have had about 30 dying in that first
90 days according to the rate at which they
died afterward. So, there’s something fishy
about that.”
In a personal interview with Dr. Ewan
Cameron, he said of the Mayo study:25
“They give a drug in tolerable doses
for a particular period of time and then suddenly stop it. If they don’t see significant results they go to the next drug and so on. That’s
not how to test vitamin C. We’re talking about
a totally different therapy. We’re talking about
something that supports the patient for the rest
of his life, not for ten weeks, which was what
the Mayo clinic did. Then they stopped it
abruptly and gave them 5FU.”
Vitamin C in the Prevention of
Cancer: Epidemiological Evidence
There is considerable epidemiological
evidence pointing to the benefits of vitamin C
in the prevention of a number of types of cancer. Unfortunately, epidemiological evidence
is often difficult to assess since general dietary
factors are difficult to pinpoint. For instance,
is high fruit consumption indicative of a high
vitamin C intake – or is it the fiber that is the
key? In addition, frequently the studies report
the effects of a number of antioxidants without separating the results for each. The following examines epidemiological evidence
according to site of primary tumor.
Bladder: Interest in vitamin C and
cancer of the lower urinary tract, including the
bladder, stems in part from the discovery that
dye-workers exposed to certain carcinogens
in the workplace (which oxidize to endogenous
orthohydroxy and hydroxylamine derivatives)
were more likely to develop bladder cancer. It
was hypothesized by at least one group of
researchers that higher levels of ascorbate in
the urine might prevent the oxidation of these
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no significant association between vitamin C
supplementation and decreased breast cancer
risk. To make the claim as they did, however,
that supplementation with vitamin C does not
confer protection from breast cancer, is
erroneous since their “higher doses” were an
average of 165.3 mg daily. (The group was
divided according to supplemental intake as
reported on a questionnaire into quintiles with
the average reported intake of vitamin C daily
ranged from 58.6 mg in the lowest quintile to
165.3 mg in the highest).35
A study to compare the 5-year survival
rates of women diagnosed in the early stages
of breast cancer who were supplemented with
3 grams daily ascorbate, with a similar group
who was not supplemented, found similar 5year survival rates in both groups.36 Since the
prognosis for women with breast cancer which
is detected early is quite good in general, this
is not surprising, as you would expect a good
prognosis, with or without ascorbate supplementation.
In an animal study, the effect of selenium in the form of sodium selinite on protection from mammary tumorigenesis was interfered with by high doses of vitamin C, while
the effect of seleno-DL-methionine was not
affected by vitamin C.37
Cervical Cancer: A Latin American
study compared nutrient intake and dietary patterns of 748 cervical cancer patients with 1,411
controls.38 The results supported a protective
affect of vitamin C against invasive cervical
cancer. Other researchers have found a similar inverse relationship between cervical neoplasia and dietary vitamin C.39,40 A review article examining a number of studies concluded
that in many, but not all studies, an inverse
relationship between vitamin C status and risk
for cervical dysplasia was observed.41
Colorectal Cancer: Colonic polyps are
recognized as a frequent precursor to colorectal
cancer. In a group of 36 patients with polyps,
19 received 3 grams ascorbate daily and 17
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Vitamin C & Cancer
carcinogens. They found that a dosage of 300
mg vitamin C in the form of 3 glasses of orange
juice daily raised urinary ascorbate to a level
capable of preventing, at least to some degree,
the oxidation (or activation) of these
carcinogens.26 The most important known risk
factor for the development of bladder cancer
is cigarette smoking.27 It is interesting to note
that cigarette smokers tend to be lower in
serum ascorbate than non-smokers.
An epidemiological study in Hawaii
comparing 195 males and 66 females with
cancer of the lower urinary tract with two
matched controls each found a decreasing risk
of cancer with increasing levels of vitamin C
consumption for women but not for men.28
Another group of researchers noted low serum ascorbate levels in the majority of 35 patients with bladder cancer.29
Breast Cancer: Plasma levels of ascorbate were significantly lower while platelet
levels were higher in a group of recently diagnosed breast cancer patients when compared
to a matched group of controls.30 Epidemiological studies appear to point to ascorbate as
a possible chemopreventive for breast cancer.
In the Iowa Women’s Health Study, women
who reported consuming at least 500 mg vitamin C daily had a relative risk of developing
breast cancer of 0.79 (not statistically significant), compared with women who did not
supplement with vitamin C.31 Rohan et al reported a small, statistically insignificant decrease in risks with vitamin C consumption
(as assessed by dietary reporting).32 In a Spanish study comparing vitamin C intake among
breast cancer patients and matched controls,
the patients reported significantly lower intakes of dietary vitamin C than controls.33
A meta-analysis of 12 studies and a
number of different nutrients and their
relationship to breast cancer found “vitamin
C intake had the most consistent and
statistically significant inverse association with
breast cancer risk.”34 Verhoeven et al found
received placebo. The researchers noted a
decrease in polyp area after nine months of
treatment with ascorbate but not placebo. In
addition, a trend toward decrease in polyp
number was noted.42 Other researchers have
used antioxidants to prevent recurrence of
polyps in patients who had undergone surgical
removal of their polyps. Patients were divided
into three groups receiving either lactulose, a
combination of vitamins A, C, and E, or
nothing. Among 209 patients, polyps recurred
in 5.7 percent of those given the vitamins, in
14.7 percent of those receiving lactulose, and
in 35.9 percent of the untreated controls.43
An Australian study examining dietary
habits and incidence of colorectal cancer found
vitamin C but not A to be protective.44 A similar study on patients of a major health plan in
Los Angeles found a weak inverse relationship between supplemental and dietary vitamin C and incidence of colorectal cancer.45
Esophageal Cancer: Esophageal cancer is among the more common types found
in Lin-Xian County in northern China. Higher
levels of nitrosamines have been detected in
the gastric juices and urine of people in this
area compared to those from a low-risk area
of China. A positive correlation was found
between esophageal lesions and nitrosamine
levels. Intake of moderate doses of ascorbic
acid by Lin-Xian subjects was found to decrease urinary nitrosamines to the level detected in the low-risk area.46
The relationships of dietary and
supplemental factors with esophageal cancer
were examined in 147 males with esophageal
cancer and 264 males with other diagnoses at
Roswell Park Memorial Institute. Vitamins C,
A, and intakes of fruits and vegetables were
associated with decreased risks of esophageal
cancer.47
Leukemia: An in vitro examination of
bone marrow cells taken from patients with
acute nonlymphocytic leukemia was conducted. The cells were allowed to colonize on
agar culture. In seven of 28 patients, the num-
bers of leukemic cell colonies were reduced
to 21 percent of that of controls by the addition of ascorbate to the culture medium. Neither glutathione (similar oxidation-reduction
potential as ascorbate) or HCl (added to cause
a comparable pH reduction to ascorbic acid)
resulted in a decrease in colonization. It was
the researchers opinion that ...“suppression
was a specific effect of L-ascorbic acid and
was not due to its oxidation-reduction potential or pH change. Leukemic cells were selectively affected at an L-ascorbic acid concentration attainable in vivo while normal hemopoietic cells were not suppressed.”48
Lung Cancer: Blood samples from 139
lung cancer patients were examined for both
plasma and buffy coat ascorbate levels. Most
samples showed hypovitaminosis C below the
levels for clinical scurvy.49 Other researchers
found hypovitaminosis C in the majority of
24 lung cancer patients.29 The First National
Health and Nutrition Examination Survey related dietary habits with lung cancer risk. An
estimate of dietary vitamin C intake by 24hour recall was used. The amount of vitamin
C in vitamins was estimated (i.e., guessed to
be 60 mg in a multiple and 500 mg if taken as
a sole supplement). The researchers found a
protective effect of vitamin C (as well as vitamin E and carotenes) from dietary sources of
these vitamins but reported no added benefit
from vitamin supplementation.50
Non-Hodgkin’s Lymphoma: An epidemiological study of factors contributing to nonHodgkin’s lymphoma (NHL) in men and
women in Nebraska found a statistically significant inverse relationship between intakes
of vitamin C, carotenes, green leafy vegetables
and citrus fruits, and incidence of NHL.51
Pancreatic Cancer: A review of the
epidemiological evidence of a dietary link to
pancreatic cancer reported consistent inverse
relationships between vitamin C and fiber, and
the incidence of pancreatic cancer.52
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Copyright©1998 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission
Safety of Vitamin C
Due to the popularity of vitamin C as
a nutritional supplement, a rash of potentially
harmful side-effects have been reported, including: calcium oxalate kidney stones, B-12
destruction, iron overload, and elevated urinary uric acid. Although reports have been contradictory, an extensive literature search
yielded a lack of support for these effects in
healthy individuals. 59 Ingestion of large
amounts of vitamin C results in only small
increases in urinary oxalates60 or urates.61 Until more information is available it is probably
prudent to avoid high doses of ascorbate in
calcium oxalate stone formers, with patients
on dialysis or with serious kidney disease,1 and
possibly in patients with hemochromatosis and
other iron overload diseases.3
Cameron and Campbell reported on
the catastrophic effect of vitamin C in a certain sub-population of terminal cancer patients.
These patients suffered from widely disseminated metastasis and the administration of high
doses of ascorbate provoked tumor hemorrhage and necrosis, resulting in the destruction of the tumor but the concomitant death of
the patient.13
Recently, a team of researchers in
England reported in a one-page scientific
correspondence to the journal, Nature, that
higher dosages of vitamin C (500 mg daily)
could actually have a pro-oxidant, rather than
an antioxidant effect by reacting with metal
ions in DNA. They found that while the blood
samples from patients supplemented with
vitamin C showed antioxidant effects on
guanine, the oxidation of another purine,
adenine, seemed to be increased. 62 They
concluded that vitamin C can be dangerous.
Certainly vitamin C has the potential to
produce free radicals in the form of ascorbyl
radicals in the same way that vitamin E forms
tocopheryl radicals. A symbiotic relationship
occurs with each quenching the other’s
radicals. Thus, administration of high doses
Alternative Medicine Review ◆ Volume 3, Number 3 ◆ 1998
Page 183
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Vitamin C & Cancer
Reticulum Cell Sarcoma: Cameron et
al reported on a case of disseminated reticulum cell sarcoma successfully treated with
high dose ascorbate. Within 10 days of beginning treatment the patient felt subjectively
much better and subsequent chest x-rays indicated he had gone into remission. When ascorbic acid was discontinued, reactivation of the
disease coincided. A second but slower complete remission occurred when vitamin C was
reinstated.53
Salivary Cancer: A case-control study
conducted in the San Francisco area examined
dietary effects on incidence of salivary gland
cancer. When 141 patients with salivary gland
cancer were compared to 271 controls, it was
determined that vitamin C intake of greater
than 200 mg daily compared to 100 mg daily
or less resulted in a 60 percent decrease in incidence of salivary gland cancer.54
Stomach/Gastrointestinal Cancer:
There are normally high levels of ascorbic acid
in the gastric mucosa and gastric juices, suggesting that vitamin C might play an important metabolic role in the stomach. 55
Helicobacter pylori has been implicated as a
risk factor for gastric cancer. In a group of 88
dyspeptic patients, 58 tested positive for H.
pylori. Gastric juice vitamin C levels were
examined in these patients as well as in the H.
pylori-negative patients. Gastric ascorbate levels were significantly lower in the H. pyloripositive group when compared both with the
negative group and to themselves after eradication of the bacteria.56
Cohen and associates examined epidemiological studies and found 9 of 10 case-control studies and 10 of 11 non-controlled studies yielded a significant inverse relationship
between ascorbic acid intake and stomach cancer risk.57 Administration of vitamin C to patients with asymptomatic peptic ulcer disease
resulted in a decrease in DNA damage in 28
of 43 subjects.58
of vitamin C may best be accompanied by
vitamin E. In addition, the fact that adenine
was oxidized may have nothing to do with the
ascorbic acid and everything to do with the
test procedures. Jenner et al, reported frequent
artifactual oxidation of DNA bases unless
specific precautions are taken.63
Conclusions
Vitamin C in high dosages appears to
be safe for the majority of individuals. Extensive epidemiological evidence points to the
capacity of ascorbic acid to prevent cancer at
a number of sites. In addition, some of the limited studies which have been conducted on the
use of high dose ascorbate in the treatment of
cancer have yielded promising results. While
vitamin C alone may not be enough of an intervention in the treatment of most active cancers, since it appears to improve quality of life
and extend survival time, it should be considered as part of a treatment protocol for all patients with cancer, whether they have chosen
a primarily orthodox, alternative medical, or
complementary approach.
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